The overall objective of this research is to identify the mechanisms mediating the proliferation and differentiation of hemopoietic stem cells. Specifically, we wish to find out how cancer, radiation, and/or chemotherapy interact with these mechanisms to produce bone marrow failure. The studies will be carried out in tumor-bearing mice so that the suppressive effects of cancer can be related to the body burden of tumor cells and the rate of tumor growth. Measurements of erythrokinetics, erythropoietin effects, and stem cell kinetics will be undertaken. When the effects of extramedullary and intramedullary tumor on the production of blood are better delineated, we will study the interaction of radiation and/or chemotherapeutic agents in tumor-bearing mice. In addition to studies of the effects of cancer and its therapy on hemopoietic stem cells and humoral inducers of differentiation, e.g. erythropoietin, we wish to study the effects of radiation and chemotherapeutic agents on the bone marrow stromal components of the hemopoietic microenvironment. There is good evidence that damage to this component of hemopoiesis by therapy or tumor may contribute to the bone marrow failure that prevents the administration of curative regimens to many patients with cancer. Information from this work will permit the design of methods to ameliorate hemopoietic insufficiency in patients treated for malignant disease.